Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor‐cleaving protease

Fontana, Stefano; Gerritsen, Helena E.; Hovinga, Johanna A. Kremer; Furlan, Miha; Lämmle, Bernhard

doi:10.1046/j.1365-2141.2001.02704.x

Cited by 76 publications

(64 citation statements)

References 12 publications

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“…Nevertheless, it is also evident from our study that slightly decreased (25%-50%) or moderately decreased ADAMTS13 activity (10%-25%) is rather common in thrombocytopenic patients with severe sepsis or HIT, a finding that is compatible with the observation of mild ADAMTS13 deficiency in various inflammatory disease states 17 and in patients with metastasizing neoplasia 20 or neoplasia-associated thrombotic microangiopathy. 21 Even though very low ADAMTS13 activity (Ͻ 5% of the activity in NHP) is a specific feature of the clinical condition labeled TTP, the sensitivity of this laboratory finding for the diagnosis of TTP remains questionable. Although, in retrospective studies, Tsai and Lian 5 observed severe ADAMTS13 deficiency in 37 of 37 patients and Furlan et al 4 in 26 of 30 patients with a diagnosis of acute TTP, the prospective study by Veyradier et al 7 found a severe deficiency in only 47 of 66 patients presenting with idiopathic or secondary TTP (sensitivity, 71%).…”

Section: Resultsmentioning

confidence: 99%

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Bianchi

Robles

Alberio

et al. 2002

Blood

301

231

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A severe deficiency in von Willebrand factor-cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n ‫؍‬ 17), heparin-induced thrombocytopenia (n ‫؍‬ 16), idiopathic thrombocytopenic purpura (n ‫؍‬ 10), or other hematologic (n ‫؍‬ 15) or miscellaneous conditions (n ‫؍‬ 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (< 30%), but none had less than 10%. Thus, the study showed that AD-AMTS13 activity is decreased in a substantial proportion of patients with thrombocytopenia of various causes. A severe deficiency of ADAMTS13 (< 5%), identified in more than 120 patients during 1996 to 2001 in our laboratory, is specific for a thrombotic microangiopathy commonly labeled TTP. (Blood. 2002;100:710-713)

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Section: Resultsmentioning

confidence: 99%

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Bianchi

Robles

Alberio

et al. 2002

Blood

301

231

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“…Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; TMA, thrombotic microangiopathy. measurable in most cases [24,25], suggesting that ADAMTS13 dysfunction is not the prominent abnormality involved in cancer-associated TMA pathophysiology. A mild to moderate decrease in ADAMTS13 activity was observed in four cases.…”

Section: Discussionmentioning

confidence: 99%

Cancer Awareness in Atypical Thrombotic Microangiopathies

et al. 2009

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After completing this course, the reader will be able to:1. Outline the clinical and biological features that would prompt a clinician to investigate an underlying malignancy in a patient suffering from thrombotic microangiopathy.2. Conduct additional investigation to diagnose or rule out malignancy.3. Formulate in timely fashion an adapted treatment plan for a patient with a cancer-associated thrombotic microangiopathy.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME The Oncologist CME Program is located online at http://cme.theoncologist.com/. ABSTRACTTo take the CME activity related to this article, you must be a registered user. Cancer BiologyThe

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“…The assumption that VWF-cleaving protease deficiency is specific for TTP has also been challenged by Oleksowicz et al, 24 who found a severe deficiency of the protease in patients with metastatic malignancies in the absence of TTP, even though others have found normal or slightly reduced protease levels in similar patients. 25 Our study, carried out in a broad inclusive population of healthy controls from newborns to elderly and in several physiologic inflammatory and disease states, demonstrates that the protease is low or very low in an array of clinical conditions unrelated to TTP, even though it was completely unmeasurable only in the 2 patients with chronic relapsing TTP.…”

Section: Discussionmentioning

confidence: 99%

Changes in health and disease of the metalloprotease that cleaves von Willebrand factor

Mannucci

Canciani

Forza

et al. 2001

Blood

461

348

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Congenital or immunomediated deficiencies of the metalloprotease that cleaves physiologically von Willebrand factor (vWF) reduce or abolish the degradation of ultralarge vWF multimers that cause the formation of intravascular platelet thrombi in patients with thrombotic thrombocytopenic purpura (TTP). There is little knowledge on the behavior of the protease in other physiological and pathologic conditions. Such knowledge is important to evaluate the specificity of low protease plasma levels in the diagnosis of TTP. Using an enzyme immunoassay, the protease was measured in 177 control subjects of different ages, in 26 full-term newborns, and in 69 women during normal pregnancy. Because TTP is often associated with multiorgan involvement and acute phase reactions, clinical models of these pathologic conditions were also investigated, including decompensated liver cirrhosis (n ‫؍‬ 42), chronic uremia (n ‫؍‬ 63), acute inflammatory states (n ‫؍‬ 15), and the preoperative and postoperative states (n ‫؍‬ 24). Protease levels were lower in healthy persons older than 65 than in younger persons. They were low in newborns but became normal within 6 months, and they were lower in the last 2 trimesters of pregnancy than in the first. Protease levels were also low in patients with cirrhosis, uremia, and acute inflammation, and they fell in the postoperative period. There was an inverse relation between low protease and high plasma levels of vWF antigen and collagen-binding activity. In conclusion, low plasma levels of the vWF cleaving protease are not a specific beacon of TTP because the protease is also low in several physiological and pathologic conditions. (Blood. 2001;98:2730-2735)

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Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor‐cleaving protease

Cited by 76 publications

References 12 publications

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Cancer Awareness in Atypical Thrombotic Microangiopathies

Changes in health and disease of the metalloprotease that cleaves von Willebrand factor

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